title: Long-lasting effects of neonatal pentobarbital administration on spatial learning and hippocampal synaptic plasticity.
abstract: Exposure of newborn rats to antiepileptics such as barbiturates has long-lasting detrimental effects on the hippocampus and hippocampus-dependent behavior. However, the long-term consequences of neonatal administration with barbiturates on the hippocampal synaptic plasticity remain unresolved. In this study, we investigated the long-lasting effects of a neonatal administration of pentobarbital on spatial memory, paired-pulse plasticity in the population spikes, and long-term potentiation (LTP) in the hippocampal CA1 region of rats in vivo. Eight weeks after administration of pentobarbital (10 or 20mg/kg) on the seventh postnatal day (P7), rats showed impaired induction in LTP. During paired-pulse stimulation, pentobarbital-treated rats exhibited a greater facilitation of the test pulse population spike, suggesting a disruption in the inhibitory GABAergic synaptic transmission. Spatial learning in hidden platform task of the Morris water maze was impaired in pentobarbital-treated rats. Our present findings indicate that neonatal treatment with pentobarbital causes alterations in function of the hippocampal inhibitory synaptic transmission that persist into adulthood, likely contributing to the long-lasting abnormalities in the hippocampal LTP as well as learning ability. We also demonstrated significant respiratory disturbances, i.e., severe hypoxia, hypercapnia, and extracellular acidosis, in rats treated with pentobarbital on P7. Given that extracellular acidosis can also modulate synaptic transmission in the developing hippocampus, this finding led us to speculate regarding the influence of respiratory disturbances in pentobarbital-induced long-lasting hippocampal dysfunctions.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan. shibak@med.hokudai.ac.jp
authors.forename: Kaori
authors.initials: K
authors.lastname: Tachibana
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Rui
authors.initials: R
authors.lastname: Kato
authors.forename: Kenkichi
authors.initials: K
authors.lastname: Tsuruga
authors.forename: Ryoko
authors.initials: R
authors.lastname: Ito
authors.forename: Yuji
authors.initials: Y
authors.lastname: Morimoto
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004594:Electrophysiology; D018757:GABA Modulators / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects*; D018782:Maze Learning / Q000187:drug effects*; D009473:Neuronal Plasticity / Q000187:drug effects*; D010424:Pentobarbital / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013037:Spatial Behavior / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D018757:GABA Modulators; D010424:Pentobarbital